Relapsing-remitting Multiple Sclerosis Research Articles

Quantitative Susceptibility Mapping Values Quantification in Deep Gray Matter Structures for Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to investigate the role of magnetic susceptibility (χ) in deep gray matter (DGM) structures, including the putamen (PUT), globus pallidus (GP), caudate nucleus (CN), and thalamus, in the most common types of multiple sclerosis (MS) and relapsing-remitting MS (RRMS), using quantitative susceptibility mapping (QSM). The literature was systematically reviewed up to November 2023, adhering to PRISMA guidelines. This study was conducted using a random-effects model to calculate the standardized mean difference (SMD) in QSM values between patients with RRMS and healthy controls (HCs). Publication bias and risk of bias were also assessed. Nine studies involving 1074 RRMS patients with RRMS and 640 HCs were included in the meta-analysis. The results showed significantly higher QSM (χ) values in the PUT (SMD = 0.40, 95% confidence interval [CI] = 0.22-0.59, p =.000), GP (SMD = 0.60, 95% CI = 0.50-0.70, p =.00), and CN (SMD = 0.40, 95% CI = 0.15-0.66, p =.005) of RRMS patients compared to HCs. However, there were no significant differences in the QSM values in the thalamus between patients with RRMS and HCs (SMD = -0.33, 95% CI -0.67-0.01, p =.026). Age- and sex-based subgroup analysis demonstrated that younger patients (<40 years) in the PUT, GP, and CN groups and larger male populations (>25%) in the PUT and GP groups had more significant χ. Interestingly, thalamic QSM values were found to decrease in RRMS patients over 40 years of age and in higher male populations. Sex-based subgroup analysis indicated higher iron levels in the PUT and GP of RRMS patients regardless of sex. QSM values were higher in certain brain regions (PUT, GP, and CN) during the early stages (disease duration <9.6 years) of RRMS, but lower in the thalamus during the later stages (disease duration >9.6 years) than HCs. QSM may serve as a biomarker for understanding χ value alterations such as iron dysregulation and its contribution to neurodegeneration in RRMS, especially in the basal ganglia nuclei including PUT, GP, and CN.

Cognitive progression independent of relapse in multiple sclerosis

Background: Substantial physical-disability worsening in relapsing-remitting multiple sclerosis (RRMS) occurs outside of clinically recorded relapse. This phenomenon, termed progression independent of relapse activity (PIRA), is yet to be established for cognitive decline. Methods: Retrospective analysis of RRMS patients. Cognitive decline was defined using reliable-change-index cut-offs for each test (Symbol Digit Modalities Test, Brief Visuospatial Memory Test–Revised, California Verbal Learning Test–II). Decline was classified as PIRA if the following conditions were met: no relapse observed between assessments nor within 9 months of cognitive decline. Results: The study sample (n = 336) was 80.7% female with a mean (standard deviation (SD)) age, disease duration, and observation period of 43.1 (9.5), 10.8 (8.4), and 8.1 (3.1) years, respectively. A total of 169 (50.3%) subjects were cognitively impaired at baseline relative to age-, sex-, and education-matched HCs. Within subjects who experienced cognitive decline (n = 167), 89% experienced cognitive PIRA. A total of 141 (68.1%) cognitive decline events were observed independent of EDSS worsening. Cognitive PIRA was more likely to be observed with increased assessments (p < 0.001) and lower assessment density (p < 0.001), accounting for baseline clinical factors. Conclusion: These results establish the concept of cognitive PIRA and further our understanding of progressive cognitive decline in RRMS.

9-HODE associates with thalamic atrophy and predicts white matter damage in multiple sclerosis

BackgroundMultiple sclerosis (MS) is characterized by extensive tissue damage leading to a range of complex symptoms, including physical disability and cognitive dysfunction. Recent work has indicated the clinical relevance of bioactive lipid mediators (LMs), which are known to orchestrate inflammation and its resolution and are deregulated in MS. However, it is unknown whether LM profiles relate to white matter (WM) damage. ObjectivesTo investigate the potential association between plasma-derived LMs and MRI-quantified WM damage using fractional anisotropy (FA) and grey matter (GM) atrophy in dimethyl fumarate-treated relapsing remitting MS (RRMS) patients. MethodsSeverity of FA-based WM damage and GM atrophy was determined in RRMS patients (n=28) compared to age- and sex-matched controls (n=31) at treatment initiation (baseline) and after 6 months. Plasma LMs were assessed using HPLC-MS/MS and baseline LMs were correlated to changes in FA and brain volumes. ResultsWe observed significant WM damage in RRMS patients (mean age 41.4 [SD 9.1]) at baseline and follow-up (z-score=-0.33 and 0.31, respectively) compared to controls (mean age 41.9 [SD 9.5]; p<0.001 for both comparisons). Patients with severe WM damage showed a decline of thalamic volume (p=0.02), and this decline correlated (r=0.51, p<0.001) with lower baseline levels of 9-HODE. This LM also predicted FA worsening (beta=0.14, p<0.001) over time at 6 months. ConclusionDespite the relatively small sample size, lower baseline levels of the LM 9-HODE correlated with more thalamic atrophy and predicted subsequent worsening of WM damage in RRMS patients.

Treatment effect modifiers of immunotherapies for relapsing-remitting multiple sclerosis—A systematic review and meta-analysis

Treatment effect modifiers of immunotherapies for relapsing-remitting multiple sclerosis—A systematic review and meta-analysis

Serum Vitamin D3 as a Potential Biomarker for Neuronal Damage in Smoldering Multiple Sclerosis

Permanent inflammatory demyelinating and neurodegenerative processes lead to neurological disability in patients with multiple sclerosis (MS). The anti-inflammatory properties of vitamin D3 (VitD) are well established, but its role in neurodegeneration is still uncertain. The usefulness of the serum concentration of VitD as a potential biomarker in evaluating brain injury in terms of recently known smoldering MS was under consideration. Methods: We assessed the concentrations of the parameters of brain injury (NF-H, GPAF, S100B, UCHL1) in the cerebrospinal fluid (CSF) of relapsing-remitting (RRMS, n = 123) and progressive MS (PMS, n = 88) patients in the group with normal levels of VitD (VitDn) and in the VitD deficiency group (VitDd). The levels of NF-H and UCHL1 were higher in the group of VitDd compared to VitDn. The higher serum levels of VitD were correlated with lower concentrations of GFAP, NF-H and S100B in the CSF of the whole group of MS patients and in women with MS as opposed to the levels of UCHL1. In men, there were noted negative correlations between the levels of serum VitD and GFAP and NF-H in CSF but not between VitD and S100B and UCHL1. The negative correlations were observed between VitD and the selected parameters of brain injury in MS patients, in women as well as in men. The concentrations of serum VitD together with selected parameters of brain injury in CSF seem to be promising biomarkers of neurodegeneration processes in smoldering MS.

Picturing the Multiple Sclerosis Patient Journey: A Symptomatic Overview.

Background: Multiple sclerosis (MS) presents a wide range of clinical symptoms, historically understood through long-term studies of earlier patient cohorts. However, due to improved diagnostic criteria, modern patients are diagnosed earlier and benefit from effective treatments, altering the disease's natural history. This study aimed to assess the clinical symptoms of MS patients in a modern population at various stages: before diagnosis, at diagnosis, during the disease course, and at the time of the survey. Methods: This was an observational study with retrospective and cross-sectional components; patients that fulfilled the 2017 revised McDonald criteria for MS completed a survey evaluating demographic and clinical data. Results: We included 163 patients, 69.9% female, with a mean age of 48.21 years; 87.1% had relapsing-remitting MS (RRMS), with a median EDSS of 2.0. Before diagnosis, 74.2% of patients experienced symptoms, mainly sensory issues (39.3%), fatigue (29.4%), and imbalance (27%). Motor and coordination symptoms were more common in progressive forms. At diagnosis, sensory (46.6%) and motor complaints (36.8%) were most prevalent. In RRMS and secondary progressive MS (SPMS), sensory and motor complaints predominated alongside imbalance, while primary progressive MS (PPMS) was characterized by motor, imbalance, and genitourinary symptoms. Throughout the disease, sensory symptoms were most common (76.1%), with fatigue (73%) and motor issues (62.6%) more prevalent in progressive forms. At the time of the survey, 50.7% of RRMS patients were asymptomatic, while progressive patients continued to experience motor symptoms, imbalance, and fatigue. Conclusions: The study reflects the modern spectrum of MS symptoms, consistent with previous research.

Providing Emotional Support During the Process of Multiple Sclerosis Diagnosis (PrEliMS): A Feasibility Randomised Controlled Trial.

To evaluate the feasibility and acceptability of an emotional support programme for newly diagnosed people with multiple sclerosis. Three-arm, mixed methods, randomised controlled trial comparing usual care, versus usual care plus nurse-specialist support, versus usual care plus nurse-specialist support plus peer support. Community-dwelling adults within two years of diagnosis or undergoing diagnosis. PrEliMS involves information provision, emotional support, and strategies and techniques based on psychoeducation, Acceptance and Commitment Therapy principles, supportive listening. One version of the intervention was provided by nurse-specialists alone and the other was provided by nurse-specialists plus peer support. The main outcome of interest was the feasibility of proceeding to a definitive trial, exploring recruitment rate, acceptability, completion of outcome measures (perceived stress, mood, self-efficacy, psychological impact, and service use), and signal of efficacy. Of 40 participants randomised (mean age 36.2 years (SD = 14.8); 54% women; 85% with relapsing-remitting MS), 36 and 38 returned 3- and 6-month questionnaires, respectively. Participant interviews suggested the trial was largely feasible, and the intervention acceptable, with some amendments to trial procedures and intervention delivery noted. There were, however, no statistically significant differences between groups at followup for any measures, and effect-size estimates were small. A definitive trial combining nurse-specialist and peer support adjustment to diagnosis intervention is warranted, but more work exploring the delivery and fidelity of the intervention is needed before this is pursued.

In multiple sclerosis patients a single serum neurofilament light chain (sNFL) dosage is strongly associated with 12months outcome: data from a real-life clinical setting.

Neurofilament light chain (NFL) is a neuroaxonal cytoskeletal protein released into cerebrospinal fluid (CSF) and eventually into blood upon neuronal injury. Its detection in serum (sNFL) makes it a promising marker in multiple sclerosis (MS). To evaluate the usefulness of a single dosage of sNFL in clinical practice. 626 consecutive relapsing-remitting (RR) MS patients treated with disease modifying treatments (DMTs) for at least 12months underwent a single sNFL dosage. 553 patients had NEDA-3 status (no relapses, no disability progression, no new/enlarging or contrast-enhancing lesions on brain magnetic resonance imaging) in the 12months prior blood sampling. sNFL levels were measured by single molecule array (Simoa™). Association between sNFL levels and NEDA-3 status at 12, 24, and 36months was evaluated with logistic regression models adjusted for sex, EDSS, disease duration, and type of DMTs. 469 out of the 553 NEDA-3 patients had normal sNFL level, whereas 42 had elevated level. The two groups did not differ regarding baseline characteristics. A very strong association between elevated sNFL levels and loss of NEDA-3 status within 12months was found, with an odds ratio [OR] of 10.74 (95% CI 4.34-26.57); 15 and 10 patients with normal and elevated sNFL, respectively lost NEDA-3 (p < 0.001). The effect was not detected during the subsequent 13-24 and 25-36months. A single elevated sNFL is strongly associated with NEDA-3 loss within 1year. Elevated sNFL in apparently stable patients suggests an ongoing disease activity below the detection threshold of standard parameters.

Suicidal ideation in the year following diagnosis of relapsing-remitting multiple sclerosis: A longitudinal perspective

IntroductionSuicidal ideation (SI) is common in people with multiple sclerosis (pwMS) who have longstanding illness. Prevalence of SI in the weeks to months following diagnosis is unknown, as are factors associated with SI, and whether SI ‘settles’ over time for newly diagnosed individuals. MethodsWe investigated SI in the FutureMS cohort, a nationally-representative relapsing-remitting MS sample (n = 440) recruited within weeks of diagnosis. SI was considered soon (‘baseline’; median 60 days) and 12 months after diagnosis. A validated mood screen classified individuals SI/non-SI. We analysed associations of clinico-demographic variables with SI and change in SI status. ResultsSI was present in 12.8 % (95 % CI = 0.10, 0.16) at baseline. Those with SI had greater disability and were more likely to be anxious, depressed, fatigued, report toileting difficulties and spasms. In regression analysis, baseline SI was associated with anxiety (p < 0.001) and depression (p = 0.002), though 16 % of those reporting SI scored just ‘mild’ for depression. At 12 months, 9.6 % (95 % CI = 0.07, 0.13) reported SI, non-significantly different than baseline. Individuals with poorest SI outcomes over 12 months had greater unemployment, disability, anxiety, depression, fatigue, toileting difficulties and spasms, but in regression analysis no variable was individually associated with SI change. LimitationsSI is complex but measured in this study by single-item question. ConclusionSI soon after MS diagnosis is relatively common, not only when anxiety and depression are present, but also in individuals with only mild depression. Screening for SI is important, allowing clinicians to target support to newly diagnosed individuals.

Depression and sedentary behaviour in women with multiple sclerosis

Depression affects around 50% of people with Multiple Sclerosis (pwMS) during their lifetime. PwMS are typically less physically active and spend twice as much time engaging in sedentary behaviour compared to the general population. Therefore, a better understanding of the factors associated with depression in pwMS, as well as the relationship between depression and sedentary behaviour and physical activity, is crucial for developing effective therapeutic strategies MS treatment. This study aimed to investigate whether the presence of depressive symptoms in pwMS is related to a longer duration of sedentary behaviour. Specially, the study assessed the relationship between depression and sedentary behaviour in women with relapsing-remitting MS (RRMS). The sample for this cross-sectional study consisted of 78 women, including 38 with relapsing-remitting MS (RRMS) (EDSS 1 to 3) and 40 healthy women. The study evaluated the depression and time in sedentary behaviour, levels of physical activity and subjective fatigue in three groups: women without MS (CG), women with MS and depression (MSD), and women with MS without depression (MSND). We found significant differences in sedentary behaviour time when comparing the group of women with MS to the group with MS and depression. The logistic regression analysis presents depression as a factor associated with sedentary behaviour in women with MS. This association became even stronger after adjustment in the multivariate model (odds ratio=1.62; 95% CI (1.13-2.64); p=0.021). Despite no differences in clinical disabilities (EDSS) or physical activity levels between the two MS subgroups (MSD and MSND), we observed a longer duration of sedentary behaviour among participants with MS and depression. There was no association with the level of physical activity. This suggests a relationship between depression and sedentary behaviour in women with MS, independent of the level of physical activity. Prolonged sedentary behaviour is a risk factor for other comorbidities, including cardiovascular disease, highlighting the importance of addressing both depression and sedentary behaviour in the management of MS. Studies that examine the amount of time pwMS spend in sedentary behaviour in various countries are crucial for developing more effective strategies tailored to different ethnicities and cultures.

MiR-98 and miR-629 can be used as a potential biomarker on relapsing-remitting multiple sclerosis patients

IntroductionMultiple Sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS), characterized by chronic inflammation, demyelination, and neurodegeneration. In recent years, among non-coding RNAs miRNA have emerged as key regulators of different biological processes and it has been suggested that they play an important role in the mechanisms underlying MS pathogenesis. Through in silico methods, miR-629-5p and miR-98-5p were identified as significant factors in MS pathology. The aim of this study was to examine the levels of expression of miR-629-5p and miR-98-5p in blood samples obtained from patients with relapsing–remitting MS. Methods: Total blood were recruited from RRMS and control group and qPCR analysis was used for evaluating of target miRNAs expression. The mirDIP database was utilized to identify the target genes. Hub genes were identified with the Cytoscape and target pathways were identified using the STRING. Results: Expression analysis revealed a significant upregulation of miR-629-5p and miR-98-5p (FC ≥ 1.5 and p < 0.05) in patients with RRMS. PI3K-Akt, Rap1, MAPK and FoxO signaling pathways were found as target. Discussion: The discovery of these miRNAs suggests that they may have a notable impact on MS patients by intervening on pathways involved in both the immune and nervous systems.

Personalized therapy and its side effects in patients with multiple sclerosis with depressive disorders

Depressive disorders in multiple sclerosis are the leading syndrome, but they have not been sufficiently studied. The clinical recommendations contain only a list of medications that were previously prescribed to patients with depression. To date, there is no description of the preferred groups of drugs for the treatment of depressive disorders, the starting dosage and timing of use, as well as possible adverse reactions when prescribing therapy to multiple sclerosis patients with depression. The purpose of this study is to search for optimal therapy for the relief of depressive disorders in patients with multiple sclerosis. Patients and methods: The study involved 203 patients with a confirmed diagnosis of multiple sclerosis (MS). The age of the patients at the time of examination ranged from 15 to 60 years, with the mean age of 39.7±10.91 years. Taking into account the type of course of the disease, MS patients were distributed as follows: 179 patients with relapsing remitting multiple sclerosis (RRMS) and 24 patients with secondary progressive multiple sclerosis (SPMS). The mean age of the examined patients with RRMS was 38±10 years; the duration of the disease was on average 8.23±6.57. The mean age of the onset of the disease was 30.2±10.5. The average disability index was EDSS 2.30±1.40. The age of the examined patients with SPMS was 46±9.00 years. The average age of onset of the disease was 33.33±8.02 years, and the level of disability was EDSS 5.70±0.30. All participants received multiple sclerosis disease modifying drugs (DMDs) and signed informed consent before being included in the study. The Beck's Depression Inventory was used to identify depression. The diagnosis of depressive disorder was established in accordance with the criteria of ICD-10 by a psychiatrist. Results and discussion: The choice of an antidepressant was made taking into account the type and degree of depression. Preference was given to the group of selective serotonin reuptake inhibitors (SSRIs), since MS patients poorly tolerate drugs with a strong sedative effect. Escitalopram was more often prescribed for anxiety depression, agomelatine for melancholic and hypochondriac depression, sertraline for asthenic depression, and fluvoxamine for adynamic depression. The starting dosage of the antidepressant in MS patients was almost twice as different from the dosage in the clinical recommendations for the treatment of depressive disorder. Due to the severity of neurological disorders, in a number of MS patients with the introduction of the starting dosage of an antidepressant, signs of sensitive ataxia, increased anxiety, and headaches were noted, therefore, the administration of an antidepressant was performed with slow titration. The association of side effects with periventricular foci in the frontal and parietal lobes of the brain has been revealed, which must be taken into account when prescribing therapy. Conclusion: Starting from the period of diagnosis of multiple sclerosis, patients need to be diagnosed for affective disorders, and risk factors that can cause depression need to be identified. When prescribing antidepressant therapy, it is necessary to take into account the type of depressive disorder, as well as the dosage of the drug, in order to exclude undesirable side effects.

Prognostic factors for disease activity in newly diagnosed teriflunomide-treated patients with multiple sclerosis: a nationwide Danish study

BackgroundClinicians frequently rely on relapse counts, T2 MRI lesion load (T2L) and Expanded Disability Status Scale (EDSS) scores to guide treatment decisions for individuals diagnosed with multiple sclerosis (MS). This...

The effect of alemtuzumab on neurodegeneration in relapsing-remitting multiple sclerosis: A five-year prospective mono-center study

BackgroundRelapsing-remitting multiple sclerosis (RRMS) is an inflammatory and neurodegenerative disease. After two or more short courses of alemtuzumab (ALZ), an immune reconstitution is achieved, which long-term results in reduced disease activity. We aimed to investigate the effect of ALZ on measures of neurodegeneration (i.e., brain atrophy, and retinal layer thinning). MethodsWe designed an observational prospective mono-center study in RRMS patients initiating ALZ treatment. Patients were assessed at baseline (month 0) and thereafter annually for five years with clinical measures, synthetic magnetic resonance imaging (SyMRI) and optical coherence tomography (OCT), with a re-baseline SyMRI scan and an OCT exam 24 months after initiating ALZ. Persons with neurological symptoms but without evidence of neurological disease served as symptomatic controls (SCs, n = 27). ResultsForty-nine RRMS patients were included. Baseline median expanded disability status scale [2.0 (IQR 1.5)] was unchanged during follow-up, 71 % were progression-free, 33 % achieved no evidence of disease activity-3 (NEDA-3). Between baseline and month 60, SyMRI showed a reduction of brain parenchymal fraction (BPF) and grey matter (GM) volume in patients. The BPF reduction was greater in RRMS patients than in SCs (p < 0.05), and more pronounced in patients with high pre-baseline disease activity than in those without (p < 0.01). OCT showed significant thinning of macular ganglion cell and inner plexiform layers (mGCIPL) and in peripapillary retinal nerve fiber layer (pRNFL) in patients. In contrast, absolute values of white matter (WM) volume and myelin content (MyC) quantified by SyMRI, were stable or increased after re-baseline (month 24) and up to month 60, and this increase appeared limited to patients without high pre-baseline disease activity and to patients with NEDA-3 or disability worsening during follow-up. A strong positive correlation between WM volume and GM volume at baseline was lost after ALZ intervention for their delta values, i.e., change from re-baseline (month 24) to month 60. While the positive baseline correlation between WM volume and MyC increased for their delta values, the positive baseline correlation between GM volume and MyC changed to negative for their delta values. ConclusionWe showed that neurodegeneration continued in RRMS patients under ALZ treatment, but it appeared to be limited to BPF and GM, and more pronounced in patients with disease activity. Our data suggest that patients who respond to ALZ treatment show signs of remyelination. OCT and SyMRI have potential to quantify measures of neurodegeneration that is affected by treatment intervention in RRMS.

A Real-World Experience of Rituximab: A Panacea in Therapy of Multiple Sclerosis in Low- and Middle-Income Setting.

Anti-CD20 monoclonal antibodies have received increasing attention in the past few years in the treatment of multiple sclerosis (MS). This study describes the (i) efficacy and safety of rituximab in people living with MS and (ii) assesses clinical and imaging outcomes following rituximab in MS. This is a chart review from the MS registry maintained at the institute from a University Hospital in South India. Eighty-three (M:F, 26:57) people living with MS received rituximab as immunomodulation between 2007 and 2022 with a median follow-up duration of 18 months. Fifty-nine (71%) were classified as relapsing-remitting MS, 16 (19%) were secondary progressive MS, and 8 (10%) were primary progressive MS. Seventy-two (87%) MS patients did not experience any relapse after receiving rituximab. In relapsing-remitting MS patients, the mean annualized recurrence rate dropped from 1.24 ± 1.19 to 0.16 ± 0.37. Infusion-related reaction occurred in 5 (6% of adverse events), urinary infections in 7 (8.4%), systemic infections in 3 (3%), Pneumocystis carinii pneumonia occurred in 1 (1%), and herpes zoster infection in 1 (1%) patient. Mortality was observed in 3 (3.5%) patients. While being on rituximab, 18 (22%) patients had mild COVID-19 illness and they all made complete recovery without any sequalae. Rituximab is a safe, well-tolerated, easily accessible, inexpensive, and effective therapeutic option for people with MS. Rituximab showed both clinical and radiological improvement after a median follow-up of 1.5 years. None of our patients showed any severe COVID infection nor side effects after receiving COVID vaccination.

Investigating colour vision and its structural correlates 15 years following a first demyelinating event

BackgroundWe investigated the long-term colour and contrast vision outcomes, 15 years after a first demyelinating event, with their structural correlates using optical coherence tomography (OCT) and brain MRI.MethodsPatients recruited with...

MultiSCRIPT-Cycle 1—a pragmatic trial embedded within the Swiss Multiple Sclerosis Cohort (SMSC) on neurofilament light chain monitoring to inform personalized treatment decisions in multiple sclerosis: a study protocol for a randomized clinical trial

BackgroundTreatment decisions for persons with relapsing–remitting multiple sclerosis (RRMS) rely on clinical and radiological disease activity, the benefit-harm profile of drug therapy, and preferences of patients and physicians. However, there is limited evidence to support evidence-based personalized decision-making on how to adapt disease-modifying therapy treatments targeting no evidence of disease activity, while achieving better patient-relevant outcomes, fewer adverse events, and improved care. Serum neurofilament light chain (sNfL) is a sensitive measure of disease activity that captures and prognosticates disease worsening in RRMS. sNfL might therefore be instrumental for a patient-tailored treatment adaptation. We aim to assess whether 6-monthly sNfL monitoring in addition to usual care improves patient-relevant outcomes compared to usual care alone.MethodsPragmatic multicenter, 1:1 randomized, platform trial embedded in the Swiss Multiple Sclerosis Cohort (SMSC). All patients with RRMS in the SMSC for ≥ 1 year are eligible. We plan to include 915 patients with RRMS, randomly allocated to two groups with different care strategies, one of them new (group A) and one of them usual care (group B). In group A, 6-monthly monitoring of sNfL will together with information on relapses, disability, and magnetic resonance imaging (MRI) inform personalized treatment decisions (e.g., escalation or de-escalation) supported by pre-specified algorithms. In group B, patients will receive usual care with their usual 6- or 12-monthly visits. Two primary outcomes will be used: (1) evidence of disease activity (EDA3: occurrence of relapses, disability worsening, or MRI activity) and (2) quality of life (MQoL-54) using 24-month follow-up. The new treatment strategy with sNfL will be considered superior to usual care if either more patients have no EDA3, or their health-related quality of life increases. Data collection will be embedded within the SMSC using established trial-level quality procedures.DiscussionMultiSCRIPT aims to be a platform where research and care are optimally combined to generate evidence to inform personalized decision-making in usual care. This approach aims to foster better personalized treatment and care strategies, at low cost and with rapid translation to clinical practice.Trial registrationClinicalTrials.gov NCT06095271. Registered on October 23, 2023

The patient-reported outcomes for the new brand-generic teriflunomide in relapsing-remitting multiple sclerosis

BackgroundPatient-reported outcomes (PROs) provide valuable insights into the impact of disease-modifying therapies (DMTs) on patients' daily lives and disease progression. This study evaluates treatment satisfaction and tolerability among patients using a brand-generic Teriflunomide (Tebazio®, 14 mg tablet) manufactured by Zistdaru Danesh Biopharmaceuticals. Materials and MethodsA Phase IV observational study was conducted on patients with Relapsing-Remitting Multiple Sclerosis (RRMS) who were either initiated on or switched to Teriflunomide 14 mg. The primary focus was on the medication's safety. Patient satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication [Version 1.4] (TSQM-14). Additionally, medication adherence and discontinuation rates were monitored. ResultsOf the 235 RRMS patients enrolled, participated in this study, all received the Teriflunomide treatment orally on a daily basis. Over the 18-month follow-up period, 25.96 % of patients discontinued the treatment. Discontinuation was mainly due to adverse events (11 %), lack of patient willingness to continue (12.7 %), and disease progression (4.2 %). The most commonly reported adverse events included dermatologic disorders, elevated liver enzymes, and gastrointestinal issues. TSQM-14 scores demonstrated significant improvements over the 18-month period. A high medication adherence rate of 98.1 % was also recorded. ConclusionPatients reported notable satisfaction with Teriflunomide, as reflected in their TSQM scores, which suggests a likelihood of improved patient adherence. The 14 mg brand-generic Teriflunomide was well-accepted by Iranian RRMS patients, with no significant concerns arising during the study. These findings also highlight the significance of patient-reported outcomes in DMTs, with potential benefits for adherence and clinical practice.

Brain hemodynamic responses and fall prediction in older adults with multiple sclerosis.

We examined whether brain hemodynamic responses, gait, and cognitive performances under single- and dual-task conditions predict falls during longitudinal follow-up in older adults with multiple sclerosis (OAMS) with relapsing-remitting and progressive subtypes. Participants with relapsing-remitting (n = 53, mean age = 65.02 ± 4.17 years, %female = 75.5) and progressive (n = 28, mean age = 64.64 ± 4.31 years, %female = 50) multiple sclerosis (MS) subtypes completed a dual-task-walking paradigm and reported falls during longitudinal follow-up using a monthly structured telephone interview. We used functional near-infrared spectroscopy (fNIRS) to assess oxygenated hemoglobin (HbO) in the prefrontal cortex during active walking and while performing a cognitive test under single- and dual-task conditions. Adjusted general estimating equations models indicated that higher HbO under dual-task walking was significantly associated with a reduction in the odds of reporting falls among participants with relapsing-remitting (odds ratio (OR) = 0.472, p = 0.004, 95% confidence interval (CI) = 0.284-0.785), but not progressive (OR = 1.056, p = 0.792, 95% CI = 0.703-1.588) MS. In contrast, faster stride velocity under dual-task walking was significantly associated with a reduction in the odds of reporting falls among progressive (OR = 0.658, p = 0.004, 95% CI = 0.495-0.874), but not relapsing-remitting (OR = 0.998, p = 0.995, 95% CI = 0.523-1.905) MS. Findings suggest that higher prefrontal cortex activation levels during dual-task walking, which may represent compensatory reallocation of brain resources, provide protection against falls for OAMS with relapsing-remitting subtype.

Can Selected Parameters of Brain Injury Reflect Neuronal Damage in Smoldering Multiple Sclerosis?

Inflammatory demyelination and impaired recovery processes result in permanent neurodegeneration and neurological disability in patients with multiple sclerosis (MS). In terms of smoldering MS, chronic neuroinflammation develops in the early period of the disease and leads to confirmed disability accumulation. There is a great need to identify biomarkers of neurodegeneration and disease progression. A single-center prospective observational study was performed. The median age of the patients was 40 (31-52) years. Women comprised 64% of the study population. We evaluated the concentrations of the parameters of brain injury (NF-H, GFAP, S100B and UCHL1) in the cerebrospinal fluid (CSF) and the selected interleukins (ILs) in serum of 123 relapsing-remitting MS (RRMS) and 88 progressive MS (PMS) patients. The levels of GFAP, S100B and UCHL were higher in the PMS group than the RRMS group, in contrast to the levels of NF-H. We observed a positive correlation between the selected pro-inflammatory cytokines and the parameters of brain injury. The Expanded Disability Status Scale (EDSS) score increased with GFAP and NF-H levels and was correlated with the selected ILs. The concentrations of S100B, UCHL1 and NF-H reflected the duration of MS symptoms. The levels of brain injury parameters in the CSF and the selected serum ILs in MS patients seem to be promising biomarkers to determine neurodegeneration and neuroinflammation in smoldering MS. Further studies are warranted in this respect.